Abstract P-114: PHARMACOKINETIC ANALYSIS OF UNFRACTIONATED HEPARIN IN CRITICALLY ILL CHILDREN DURING EXTRACORPOREAL MEMBRANE OXYGENATION: DO WE ACHIEVE THE TARGET?

Grimaud, Marion; Urien, Saı̈k; Borgel, Delphine; Amar, Gilles; Gaudin, Régis; Burgos, Paula I.; Tréluyer, Jean‐Marc; Renolleau, Sylvain; Oualha, Mehdi

doi:10.1097/01.pcc.0000537571.01928.c4

Cited by 3 publications

(3 citation statements)

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“…The results match with the physicochemical properties of UFH, which is considered a hydrophilic drug, hence distributing only in the intravascular space indicating the 1‐compartment PK model is a reasonable structural PK model for UFH 24 . Additionally, the results are consistent with the previous PK modeling efforts on UFH indicating that a 1‐compartment PK model adequately describes the UFH concentration–time profile 25‐29 . Adding a time‐varying component to CL significantly improved the PK model in terms of the statistical criteria and diagnostic plots.…”

Section: Discussionsupporting

confidence: 82%

“…20 The estimated typical steady-state CL value was consistent between ECMO and non-ECMO settings. 25,26,29,30 However, the consistency between CL under ECMO and non-ECMO conditions contradicts with a prior ECMO study in infants (n = 5), where UFH CL was approximately doubled during the ECMO session compared to after the decannulation procedure. 12 Considering the physicochemical properties, heparin is a hydrophilic drug that reduces the susceptibility of sequestration by ECMO circuits.…”

Section: Discussionmentioning

confidence: 66%

“…24 Additionally, the results are consistent with the previous PK modeling efforts on UFH indicating that a 1-compartment PK model adequately describes the UFH concentration-time profile. [25][26][27][28][29] Adding a time-varying component to CL significantly improved the PK model in terms of the statistical criteria and diagnostic plots. The time-varying CL can be considered biologically plausible given that the pediatric patients with severe respiratory and/or cardiac dysfunction require ECMO for oxygenation and circulation support while allowing the heart and lungs to rest and recover.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetic Modeling Using Real‐World Data to Optimize Unfractionated Heparin Dosing in Pediatric Patients on Extracorporeal Membrane Oxygenation and Evaluate Target Achievement–Clinical Outcomes Relationship

Salem

Smith

Wilkes

et al. 2023

The Journal of Clinical Pharma

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Unfractionated heparin (UFH) is a commonly used anticoagulant for pediatric patients undergoing extracorporeal membrane oxygenation (ECMO) but evidence is lacking on the ideal dosing. We aimed to: (i) develop a population pharmacokinetic (PK) model for UFH, measured through anti‐factor Xa assay, (ii) optimize UFH starting infusions and dose titrations through simulations, and (iii) explore UFH exposure‐clinical outcomes relationship. Data from 218 patients admitted to Utah's Primary Children's Hospital were retrospectively collected. A one‐compartment PK model with time‐varying clearance (CL) adequately described UFH PK. Weight on CL and volume of distribution and, ECMO circuit change on CL were significant covariates. The typical estimates for initial CL and first‐order rate constant to reach steady‐state CL were 0.57 L/(h·10 kg) and 0.02 h−1. Comparable to non‐ECMO patients, the typical steady‐state CL was 0.81 L/(h·10 kg). Simulations showed that a 75 IU/kg UFH bolus dose followed by starting infusions of 25 & 20 IU/h/kg for patients < 6 & ≥ 6 years, respectively, achieved the therapeutic target in 56.6% of all patients while only 3.1% exceeded the target. The proposed UFH titration schemes achieved the target in > 90% of patients while < 0.63% were above the target after 24 and 48 hours of treatment. The median intensive care unit survival time in patients within and below the target at 24 hours was 136 and 66 hours, respectively. In conclusion, PK model of UFH was developed for pediatric patients on ECMO. The proposed UFH dosing scheme attained the anti‐factor Xa target rapidly and safely.This article is protected by copyright. All rights reserved

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetic Modeling Using Real‐World Data to Optimize Unfractionated Heparin Dosing in Pediatric Patients on Extracorporeal Membrane Oxygenation and Evaluate Target Achievement–Clinical Outcomes Relationship

Salem

Smith

Wilkes

et al. 2023

The Journal of Clinical Pharma

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Factors Influencing Unfractionated Heparin Pharmacokinetics and Pharmacodynamics During a Cardiopulmonary Bypass

Gibert,

Lanoiselée,

Gouin-Thibault

et al. 2024

Clin Pharmacokinet

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Pharmacokinetics Alterations in Critically Ill Pediatric Patients on Extracorporeal Membrane Oxygenation: A Systematic Review

et al. 2020

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Objectives: This study aimed to identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps, and inform future pharmacology studies. Data Sources: We systematically searched the databases MEDLINE, CINAHL, and Embase from earliest publication until November 2018 using a controlled vocabulary and keywords related to "ECMO" and "pharmacokinetics," "pharmacology," "drug disposition," "dosing," and "pediatrics." Study Selection: Inclusion criteria were as follows: study population aged <18 years, supported on ECMO for any indications, received any medications while on ECMO, and reported pharmacokinetic data. Data Extraction: Clearance and/or volume of distribution values were extracted from included studies. Data Synthesis: Forty-one studies (total patients = 574) evaluating 23 drugs met the inclusion criteria. The most common drugs studied were antimicrobials (n = 13) and anticonvulsants (n = 3). Twenty-eight studies (68%) were conducted in children <1 year of age. Thirty-three studies (80%) were conducted without intra-study comparisons to non-ECMO controls. Increase in volume of distribution attributable to ECMO was demonstrated for nine (56%) drugs: cefotaxime, gentamicin, piperacillin/tazobactam, fluconazole, micafungin, levetiracetam, clonidine, midazolam, and sildenafil (range: 23-345% increase relative to non-ECMO controls), which may suggest the need for higher initial dosing. Decreased volume of distribution was reported for two drugs: acyclovir and ribavirin (50 and 69%, respectively). Decreased clearance was reported for gentamicin, ticarcillin/clavulanate, bumetanide, and ranitidine (range: 26-95% decrease relative to non-ECMO controls). Increased clearance was reported for caspofungin, micafungin, clonidine, midazolam, morphine, and sildenafil (range: 25-455% increase relative to non-ECMO controls). Sutiman et al. Pharmacokinetic Alterations in Pediatric ECMO Conclusions: There were substantial pharmacokinetic alterations in 70% of drugs studied in children on ECMO. However, studies evaluating pharmacokinetic changes of many drug classes and those that allow direct comparisons between ECMO and non-ECMO patients are still lacking. Systematic evaluations of pharmacokinetic alterations of drugs on ECMO that incorporate multidrug opportunistic trials, physiologically based pharmacokinetic modeling, and other methods are necessary for definitive dose recommendations.

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Abstract P-114: PHARMACOKINETIC ANALYSIS OF UNFRACTIONATED HEPARIN IN CRITICALLY ILL CHILDREN DURING EXTRACORPOREAL MEMBRANE OXYGENATION: DO WE ACHIEVE THE TARGET?

Cited by 3 publications

References 1 publication

Pharmacokinetic Modeling Using Real‐World Data to Optimize Unfractionated Heparin Dosing in Pediatric Patients on Extracorporeal Membrane Oxygenation and Evaluate Target Achievement–Clinical Outcomes Relationship

Pharmacokinetic Modeling Using Real‐World Data to Optimize Unfractionated Heparin Dosing in Pediatric Patients on Extracorporeal Membrane Oxygenation and Evaluate Target Achievement–Clinical Outcomes Relationship

Factors Influencing Unfractionated Heparin Pharmacokinetics and Pharmacodynamics During a Cardiopulmonary Bypass

Pharmacokinetics Alterations in Critically Ill Pediatric Patients on Extracorporeal Membrane Oxygenation: A Systematic Review

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